[eng] Human papilloma virus (HPV)-based screening provides greater protection against cervical cancer (CC) than cytology-based strategies. However, HPV tests present lower specificity to detection high-grade squamous intraepithelial lesion or CC (HSIL/CIN2+), which means following many women without infections/lesions with risk of progression to cancer.
Therefore, it is necessary to: 1) choose an HPV test that demonstrates the best sensitivity and specificity profile and 2) identify useful molecular biomarkers in the selection of HPV-positive women with risk of developing HSIL/CIN2+.
In the first study, we analyzed 5 HPV testing and genotyping techniques (Hybrid Capture 2 [HC2], AnyplexTMII HPV28, Linear Array, GP5+/6+ PCR-EIA-RH and CLART2 in 295 women referred to colposcopy due to an altered screening test. DNA extraction for HPV genotyping was performed in cervical sample specimens after Pap test and HPV detection by HC2. We included women with an adequate cervical sampling with sufficient material for the Pap test and HPV detection and genotyping and those with at least one colposcopically-directed biopsy and/or endocervical curettage. HC2 showed the highest sensitivity for HSIL/CIN2+ detection (96.1%), but all the HPV genotyping tests showed a higher specificity (76.5%-86.8%). The agreement between HC2 results and the other techniques was similar. HPV16/18 infection was a risk factor for underlying HSIL/CIN2+. Anyplex showed the highest risk of underlying HSIL/CIN2+ after positive HPV16/18 tests (OR 31.1; 95% IC 12.1-80.0).
In the second study we assessed the prognostic value HPV16/18 genotyping and p16/Ki67 dual staining cytology in HPV-positive women with no lesion or minor abnormalities. We evaluated progression HSIL/CIN2+, persistence/regression of HPV infection in 200 women referred to our unit showing HPV infection, histology diagnosis different from HSIL/CIN2+ and negative cytology. HPV genotyping and dual staining were performed in liquid-based cytological specimens obtained on the first visit. Progression was observed in 8% of the women. Those with HPV16/18 infection had an increased risk of progression compared with women infected by other HPV types and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining.
In conclusion, the HPV tests evaluated yield very high concordance and showed a similar clinical sensitivity and specificity for HSIL/CIN2+ detection. Moreover, HPV 16/18-positive women with no lesion or minor abnormalities are at high risk of progression to HSIL/CIN2+ and HPV persistence.